A longstanding theme in tetrapyrrole chemistry has been the de novo synthesis of building blocks for use in studies encompassing the broad fields of biomimetic chemistry, materials science, and clinical medicine. Porphyrins with up to four distinct meso-substituents are readily available.1,2 The chemistry of chlorins is less developed, but chlorin macrocycles with substituents at designated meso- and β-pyrrole sites have been prepared.3,4 For bacteriochlorins, synthetic access is under active development. Bacteriochlorins are of considerable interest owing to their strong absorption in the near-infrared spectral region, which is attractive for solar energy applications, low-energy photochemistry, and deep-tissue light-mediated medical therapies.5,6 Realizing the scientific potential of bacteriochlorins has been somewhat crimped, however, by the limited means for synthesis of stable, tailorable bacteriochlorin building blocks.7 
Distinct methods for the synthesis of bacteriochlorins entail semisynthesis procedures beginning with bacteriochlorophyll a;8-14 hydrogenation15,16 of (or addition to)4,17-22 synthetic porphyrins and chlorins; and de novo routes.5,23-28 Each has strengths and limitations. Representative building blocks available via such methods are shown in Chart 1. Derivatization of bacteriochlorophyll a to form the imide ring stabilizes the macrocycle and provides a convenient handle at the N-imide site for derivatization (entry I).29 Still, few other sites are available given the nearly full complement of β-substituents. meso-Tetraarylbacteriochlorins (entry II) are readily synthesized yet the presence of four identical substituents may limit the accessible architectures. Two variants on this approach include (i) a strategy by Bruckner to achieve wavelength tunability,30 and (ii) a strategy by Boyle wherein trans-AB-porphyrins undergo vicinal dihydroxylation to afford the corresponding trans-AB-bacteriochlorin building blocks (albeit composed of a mixture of diastereomers, entry III).31

A rational, de novo route to synthetic bacteriochlorins25,28 that we have been developing (see, e.g., H. Kim and J. Lindsey, De Novo Synthesis of Bacteriochlorins, U.S. Pat. No. 7,534,807) affords the following features: (1) resiliency of the macrocycles toward dehydrogenation upon routine handling by virtue of a geminal-dimethyl group in each reduced ring;25 (2) a relatively concise (8-step) synthesis;27,28 (3) characteristic bacteriochlorin absorption and photophysical features;6,32 and (4) ability to introduce a variety of β-pyrrole substituents.5,26,28 The synthetic route employs the acid-mediated, room-temperature self-condensation of a dihydrodipyrrin-acetal (Scheme 1).

The use of TMSOTf in the presence of 2,6-di-tert-butylpyridine (2,6-DTBP) results in the formation of the 5-methoxybacteriochlorin in 8.4-63% yield depending on the nature of the β-pyrrolic substituents.28 The 5-methoxybacteriochlorin BC-1 undergoes regioselective electrophilic bromination at the 15-position,33 enabling further derivatization at this site via diverse palladium-coupling processes.29,33 In contrast, bromination of the 5-unsubstituted bacteriochlorin BC-2 (available via BF3.OEt2 or other catalysis)28 results in a mixture of mono- and dibromobacteriochlorins.33 
While the de novo method has provided access to a larger palette of substituted bacteriochlorins versus those via semisynthesis or porphyrin/chlorin reductive transformations, numerous limitations persist: (1) the substituents at the 2- and 12-positions are identical with each other (R), as are those at the 3- and 13-position (R′); (2) the 5-methoxy group is either present or absent but otherwise not variable; and (3) approaches are not yet available to prepare trans-AB-bacteriochlorins akin to those of Boyle. A linear pattern of meso-AB-substituents is attractive for the design of various molecular architectures.